High levels of estrogen may help protect a woman from mood disorders, while low levels of the hormone can make a woman more susceptible to trauma at certain times in her menstrual cycle, according to new research by Harvard and Emory University neuroscientists.

Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference has remained unclear. The new research, however, suggests that women are most at risk for symptoms of post-traumatic stress disorder (PTSD) when their estrogen is low during the menstrual cycle.

“PTSD is a disorder of recovery,” said author Mohammed Milad, associate professor of psychiatry at Harvard Medical School (HMS) and director of the Behavioral Neuroscience Laboratory at Massachusetts General Hospital (MGH).

Men may be less susceptible to mood disorders since testosterone is regularly converted into estrogen in the male brain, resulting in a more steady flow of estrogen.

In healthy women and female rats, estrogen calms the fear response, according to the Harvard researchers, who were led by Kelimer Lebron-Milad, an HMS instructor of psychiatry.

The Emory researchers, led by postdoctoral researcher Ebony Glover, proved that the same is true for women suffering from PTSD. The higher their blood levels of estrogen were when they completed a fear-extinction task, the less likely women were to act startled.

Both studies used “fear-conditioning” experiments, in which the participant is trained to fear a safe “conditioned stimulus” such as a colored shape, paired with a frightening or painful “unconditioned stimulus” like a shock to the finger or a puff of air to the neck or eye.

Overall, women or female rats showed less fear to the neutral stimulus when their estrogen levels were high rather than low.

PTSD is common in women after a trauma such as rape or sexual assault, which studies say are experienced by 25 to 30 percent of women in their lifetimes, and the symptoms last on average four times as long in women as in men after trauma.

This new research suggests the reason for this vulnerability may be the monthly menstrual change in estrogen.

“People are afraid to look into the influence of sex hormones on ‘fear learning’ and extinction,” said Mohammed Milad, “because it’s such a complex system.”

When Milad studied fear as a Ph.D. student, his lab used only male rats. But when he began to study fear in humans as a postdoctoral researcher, he saw that female data were much more variable.

“The data led me there,” to sex differences, Milad said. “Since females add variance, scientists have tended to avoid studying them” in rodent research, he said. Studies of the human brain would tend to combine men and women, assuming that neurological gender differences were minimal. But this attitude is changing.

In addition, since birth control pills affect estrogen levels, they may be used as a future treatment against post-traumatic stress.

New simulators mimic the symptoms of a patient with clinical psychological disorders, according to new research presented at the American Psychological Association’s 120th Annual Convention.

“As this technology continues to improve, it will have a significant impact on how clinical training is conducted in psychology and medicine,” said psychologist and virtual reality technology expert Albert “Skip” Rizzo, Ph.D.

Technological advances including artificial intelligence and expert systems allow a highly interactive interaction with simulators even allowing the simulators to carry on a conversation with real humans.

“This has set the stage for the ‘birth’ of intelligent virtual humans to be used in clinical training settings,” Rizzo said. He showed videos of clinical psychiatry trainees engaging with virtual patients called “Justin” and “Justina.”

Justin is a 16-year-old with a conduct disorder who is being forced by his family to participate in therapy. Justina, the second and more advanced iteration of this technology, is a sexual assault victim who was designed to have symptoms of post-traumatic stress disorder.

In an initial test, 15 psychiatry residents, of whom six were women, were asked to perform a 15-minute interaction with Justina.

Video of one such interaction shows a resident taking an initial history by asking a variety of questions. Programmed with speech recognition software, Justina responds to the questions and the resident is able to make a preliminary diagnosis.

Rizzo’s virtual reality laboratory is working on the next generation of virtual patients using information from this and related user tests, and will further modify the characters for military clinical training, which the U.S. Department of Defense is funding, he said.

Researchers are working to develop simulated or virtual veterans with depression and suicidal thoughts, for use in training clinicians and other military personnel how to recognize the risk for suicide or violence.

Over time, Rizzo hopes to create a comprehensive computer training module that has a diverse library of virtual patients with numerous “diagnoses” for use by psychiatric and psychology educators and trainees.

Currently, psychology and psychiatry students are trained by role-playing with other students or their supervisors to gain experience to treat patients. They then engage in supervised on-the-job training with real patients to complete their degrees.

“Unfortunately, we don’t have the luxury of live standardized ‘actor’ patients who are commonly used in medical programs, so we see this technology as offering a credible option for clinical psychology training,” he said.

“What’s so useful about this technology is novice clinicians can gain exposure to the presentation of a variety of clinical conditions in a safe and effective environment before interacting with actual patients. In addition, virtual patients are more versatile and can be available anytime, anywhere. All you need is a computer.”

Any perception can connect us to reality, properly and fully. What we see doesn't have to be pretty, particularly; we can appreciate anything that exists. There is some principle of magic in everything, some living quality. Something living, something real, is taking place in everything. --Chögyam Trungpa Rinpoche